Sensitization of cancer cells to paclitaxel-induced apoptosis by canagliflozin.

Cancer cells consume more glucose and usually overexpress glucose transporters which have become potential targets for the development of anticancer drugs. It has been demonstrated that selective SGLT2 inhibitors, such as canagliflozin and dapagliflozin, display anticancer activity. Here we demonstrated that canagliflozin and dapagliflozin synergistically enhanced the growth inhibitory effect of paclitaxel in cancer cells including ovarian cancer and oral squamous cell carcinoma cells. Canagliflozin also inhibited glucose uptake via GLUTs. The combination of paclitaxel and WZB117, a GLUT inhibitor, exhibited a strong synergy, supporting the notion that inhibition of GLUTs by canagliflozin may also account for the synergy between canagliflozin and paclitaxel. Mechanistic studies in ES-2 ovarian cancer cells revealed that canagliflozin potentiated paclitaxel-induced apoptosis and DNA damaging effect. Paclitaxel in the nanomolar range elevated abnormal mitotic cells as well as aneuploid cells, and canagliflozin further enhanced this effect. Furthermore, canagliflozin downregulated cyclin B1 and phospho-BUBR1 upon spindle assembly checkpoint (SAC) activation by paclitaxel, and may consequently impair SAC. Thus, paclitaxel disturbed microtubule dynamics and canagliflozin compromised SAC activity, together they may induce premature mitotic exit, accumulation of aneuploid cells with DNA damage, and ultimately apoptosis.

Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer.

To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3-12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects.

Segmental ureterectomy does not compromise the oncologic outcome compared with nephroureterectomy for pure ureter cancer.

PURPOSE: Pure ureter cancers are rare and account for only 1-3 % of urothelial carcinomas with limited data. Nowadays, nephron-sparing methods are reserved mainly for imperative cases. This study intends to assess the oncologic outcome between segmental ureterectomy (SU) and radical nephroureterectomy (RNU) for pure ureteral urothelial carcinoma. METHODS: From July 2004 to August 2010, 112 patients at a single tertiary referral center were included. Perioperative data were obtained from our institutional database. Postoperative CT scan, cystoscopy, and contralateral renal echo were performed regularly for survey of disease recurrence. RESULTS: The mean length of follow-up was 43.8 and 48.3 months for the RNU and SU group, respectively. The bladder recurrences, local recurrences, distant metastasis, and cancer-specific survival rates showed no significant differences between RNU and SU (36.4 vs. 34.2 %, p = 0.83; 23.4 vs. 14.3 %, p = 0.27; and 16.9 vs. 8.6 %, p = 0.244, and 13.0 vs. 5.7 %, p = 0.249, respectively). CONCLUSION: The study suggested that SU is not inferior to RNU for ureter cancer in oncologic outcomes and is less invasive and better nephron preservation.

Intravesical drug delivery for dysfunctional bladder.

The bladder is a hollow organ that can be treated locally by transurethral catheter for intravesical drug instillation or cystoscopy for intravesical drug injection. With advancing technology, local organ-specific therapy and drug delivery is of expanding interest for treating dysfunctional bladder, including interstitial cystitis/bladder pain syndrome, overactive bladder and sterile hemorrhagic cystitis after chemotherapy or pelvic radiation. Intravesical therapy has shown varying degrees of efficacy and safety in treating interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with new modalities being developed. Intravesical (regional) therapy has several advantages than oral (systemic) therapy, including high local concentration and less systemic toxicity. In recent years, intravesical delivery of biotechnological products including neurotoxins and immunosuppressive agents, and delivery platform including liposomes has shown promise for lower urinary tract symptoms. This review considers the current status of intravesical therapy in dysfunctional bladder including interstitial cystitis/bladder pain syndrome, overactive bladder and hemorrhagic cystitis with special attention to lipid based novel drug-delivery.

High-intensity diode laser in combination with bipolar transurethral resection of the prostate: a new strategy for the treatment of large prostates (>80 ml).

BACKGROUND AND OBJECTIVE: The ideal treatment of large prostates with symptomatic benign prostatic hyperplasia (BPH) remains controversial. We compare the efficacy and safety of monopolar transurethral resection of the prostate (TURP) with high-intensity diode laser in combination with bipolar TURP (DL + b-TURP) in the treatment of large prostates. MATERIALS AND METHODS: We retrospectively analyzed all patients with lower urinary tract symptoms (LUTS) secondary to BPH with prostates larger than 80 ml, undergoing monopolar TURP (n = 36) or DL + b-TURP (n = 37) between January 2008 and March 2010. The preoperative and follow-up functional parameters including International Prostate Symptom Score (IPSS), post-void residual urine (PVR), maximum flow rate (Q(max) ), quality of life score (QoLs), prostate size, and prostate-specific antigen (PSA) were assessed. The operative data, peri- and post-operative complications were also recorded. RESULTS: The demographic data were comparable between the two groups. Preoperative prostate volume was 110.8 ± 28.9 ml in the DL + b-TURP group and 103.7 ± 31.2 ml in the TURP group. TURP group had significantly shorter operative time; however, the catheterization time and hospital stay were in favor of the DL + b-TURP group (P < 0.001). The decrease in hemoglobin was statistically significantly greater in the TURP group. Late complications were also comparable. Both groups could achieve significant improvements in functional outcomes during the follow-up of 24 months. CONCLUSIONS: With regard to the operative safety and functional results, high-intensity diode laser combined with bipolar TURP is feasible for BPH treatment with large prostates.

Efficacy and safety of photoselective vaporization of the prostate in patients with prostatic obstruction induced by advanced prostate cancer.

OBJECTIVE: We evaluated the efficacy and outcome of laser photoselective vaporization of prostate (PVP) in patients with voiding difficulty due to prostatic obstruction induced by advanced prostate cancer (PC). METHODS: We retrospectively studied the records of 13 patients with advanced PC and prostatic obstruction with a mean prostate volume of 65.0 ml. All of the 13 patients received PVP between 2006 and 2010 due to the symptoms of voiding difficulty or acute urinary retention (AUR; N = 10) refractory to medical treatment. Perioperative safety and functional results were evaluated. RESULTS: Lasering time ranged from 24 to 20 minutes (mean 67 ± 26), during which 66-423 KJ (mean 172 ± 95) of laser energy was delivered. All patients could resume voiding function with a mean catheterization time of 3.0 days. CONCLUSIONS: Our preliminary results suggest that PVP is a safe and effective procedure for relieving prostatic obstruction without intraoperative blood transfusion, water intoxication, or other complications in patients with advanced prostate cancer.

Simultaneous transurethral resection of prostate and prostate needle biopsy in patients with acute urinary retention and elevated prostate specific antigen levels.

BACKGROUND: To evaluate the safety and accuracy of simultaneous transrectal ultrasonography (TRUS)-guided prostate biopsy and transurethral resection of prostate (TURP), patients with acute urinary retention (AUR) who underwent simultaneous prostate biopsy and TURP were compared with those treated by TURP alone. METHODS: From July 2000 to Jun 2004, 21 patients older than 70 years with AUR were included in each group. Patients with elevated prostate specific antigen (PSA) levels > 4 ng(/ml) underwent TURP and TRUS-guided biopsy simultaneously (group I), while those with normal PSA levels < 4 ng(/ml) received TURP alone (group II). The average ages of group I and group II patients were 72.4 and 72.5 years. RESULTS: In group I, 4 patients (19%) were diagnosed with prostate cancer; 2 had metastasis and received hormone therapy; and 1 had localized cancer and was treated with brachytherapy. An 82-year-old patient with localized cancer opted for watchful waiting. Compared to group II, patients in group I did notshow aggregated morbidity, such as prolonged hospital stay, hematuria, or fever. CONCLUSION: Simultaneous TURP and TRUS-guided biopsy in healthy AUR patients does not increase the risk of morbidity. Furthermore, with this approach patients can recover from the stress of AUR and have a definite diagnosis of their condition.